The primary aim of this application is to establish a large registry of Australian multi-generational pedigrees. with an Operation Core at The University of Melbourne, through collecting and storing epidemiological information on the major recognized and putative risk factors, including dietary intakes, biological specimens (blood, DNA, and tumor tissue), and clinical data (tumor sub-type, grade, stage at diagnosis, hormone receptor status, treatment, clinical course). and by conducting follow-up studies. This resource will be made available to the USA and worldwide for research into the genetic epidemiology, biology, etiology, prevention and treatment of breast cancer. The pedigrees we will collect will predominately be population-based, selected through the Victorian and New South Wales Cancer Registries to which case ascertainment is considered complete, and we have 2 years experience applying the study design. Data collected by the end of 1995, including 500 control pedigrees, will be made available to the co-operative Registry, at no cost to this grant. We now seek funding to achieve: (i) 1,000 population-based families, based on early onset cases in women diagnosed before the age of 40 (about 30% of the grant); (ii) 200 population-based high-risk families containing two or more closely related individuals of either sex with breast or other breast-related cancers, based on screening about 1 ,000 women with breast cancer diagnosed between age 40 and 69; (about 40% of the grant); (iii) 700 population-based control families (at no cost to this grant); (iv) approximately 100 twin pairs in which one or both has had breast cancer, and their families (about 15% of the grant); and (v) between 50 and 100 high-risk families containing multiple cases of breast and possibly other breast-related cancers selected on an opportunistic basis through physicians, hospital-based cancer family clinics, established cancer epidemiology studies, and breast screening clinics (about 15% of the grant). Australia has many similarities with the USA, and is an excellent country in which to establish a Breast Cancer Family Registry due to its manageable yet sufficient size, ethnic diversity, highly localized, relatively stable population in which families are usually intact and in contact with one another. Moreover, we have local experience in recruitment, follow-up, epidemiological and clinical data collection, database management and statistical analysis, the ability to transport biological material and epidemiological data to researchers worldwide, and the expertise and drive to ensure the study will achieve its full potential. Genetic counselling services are established at no cost to users, translational research studies are already being carried out and some aspects will be further developed as a pilot study, and the logistics are possible through utilization of national and state databases and established professional networks.